Loss of the BCR-FGFR1 GEF Domain Suppresses RHOA Activation and Enhances B-Lymphomagenesis in Mice.

ABSTRACT: Transformation of hematopoietic stem cells by the BCR-FGFR1 fusion kinase found in a variant of stem cell leukemia/lymphoma (SCLL) syndrome leads to development of B-lymphomas in syngeneic mice and humans. In this study, we show that the relatively rapid onset of this leukemia is potentially related to oncogenic domains within the BCR component. BCR recruited a guanidine nucleotide exchange factor (GEF) domain to the fusion kinase to facilitate activation of small GTPases such as the Ras homology gene family, member A (RHOA). Deletion of this GEF domain increased leukemogenesis, enhanced cell survival and proliferation, and promoted stem cell expansion and lymph node metastasis. This suggests that, in an SCLL context, the presence of the endogenous GEF motif leads to reduced leukemogenesis

SUBMITTER: Hu T 

PROVIDER: S-EPMC6484845 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature